Apparatus and method for transporting sample well trays

ABSTRACT

An apparatus for transporting sample well trays with respect to a heating device is provided. The apparatus includes a sample well tray holder, a rotational actuator, and a biasing mechanism. The sample well tray holder includes a plate in which a sample well tray may be positioned. The sample well tray holder is configured to rotate about a first rotational axis. The rotational actuator is configured to rotate the sample well tray holder about the first rotational axis. The biasing mechanism is configured to urge the sample well tray holder in a generally upward direction along the first rotational axis.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to an apparatus and method fortransporting sample well trays. In certain embodiments, the apparatusplaces sample well trays into a heating device and removes the samplewell trays therefrom.

[0003] 2. Description of the Related Art

[0004] Biological testing has become an important tool in detecting andmonitoring diseases. In the biological testing field, thermal cycling isoften utilized in order to amplify nucleic acids by, for example,performing polymerase chain reactions (PCR) and other reactions.

[0005] It is desirable to increase the throughput of such biologicaltesting. One method for increasing throughput is to provide real-timedetection capability during thermal cycling. Providing real-timedetection increases the efficiency of the biological testing because thesamples can be tested while in the thermal cycling device, therefore notrequiring removal of the sample well tray prior to testing the samples.An additional method of increasing throughput of biological testing isto automatically load sample well trays into the heating device, performa heating operation such as thermal cycling, and then automaticallyremove the sample well tray using a robotic mechanism. However, existingrobotic mechanisms are not particularly suited for thermal cyclingdevices with real-time detection units. In particular, existing roboticmechanisms are not particularly configured for accessing the thermalcycling device without interfering with the detection units.

[0006] It is desirable to provide a sample well tray manipulatingapparatus and method that is compatible for use with thermal cyclingdevices having real-time detection units in order to increasethroughput.

SUMMARY OF THE INVENTION

[0007] The advantages and purposes of the invention will be set forth inpart in the description which follows, and in part will be apparent fromthe description, or may be appreciated by practice of the invention. Theadvantages and purposes of the invention will be realized and attainedby means of the elements and combinations particularly pointed out inthe appended claims.

[0008] In one aspect, the invention includes an apparatus fortransporting sample well trays with respect to a heating device. Incertain embodiments, the apparatus includes a sample well tray holder, arotational actuator, and a biasing mechanism. The sample well trayholder includes a plate in which a sample well tray may be positioned.The sample well tray holder is configured to rotate about a firstrotational axis. The rotational actuator is configured to rotate thesample well tray holder about the first rotational axis. The biasingmechanism is configured to urge the sample well tray holder in agenerally upward direction along the first rotational axis.

[0009] In another aspect, the invention includes a robotic manipulatorfor transporting sample well trays between at least two positions. Therobotic manipulator includes a robotic arm, a rotational mechanism, anda biasing mechanism. The robotic arm includes a sample well tray holderconfigured to support a sample well tray therein. The sample well trayholder includes a recess for the sample well tray. The rotationalmechanism is configured to impart rotational motion on the robotic arm,and includes a motor. The biasing mechanism is configured to provideforce on the sample well tray holder in a direction away from anadjacent sample block.

[0010] In a further aspect, the invention includes a system formanipulating sample well trays. The system includes a robot configuredto transport a sample well tray to a first location, a loadingmechanism, and a heating device. The loading mechanism is configured totake a sample well tray from the first location, place the sample welltray into the heating device, for example, a thermal cycler at a secondlocation and then later remove the sample well tray from the heatingdevice and return the sample well tray to the first location. Theloading mechanism includes a sample well tray holder in which a samplewell tray may be positioned therein, a rotational actuator configured torotate the sample well tray holder, and a biasing member configured tourge the sample well tray and sample well tray holder in a directionaway from a sample block. The heating device includes an opening forreceiving the sample well tray therein.

[0011] In yet another aspect, the invention includes a method ofmanipulating sample well trays. The method includes the step of placingthe sample well tray into a sample well tray holder of a first robotmechanism located at a first position. The method further includes thestep of rotating the sample well tray holder of the first robotmechanism about a rotational axis in a first rotational direction toinsert the sample well tray holder into a heating device at a secondposition. The sample well tray holder is lowered in a direction toward asample block of the heating device so that the sample well tray engagesthe sample block. After undergoing thermal cycling or other operations,the sample well tray disengages from the sample block so that the samplewell tray does not directly contact the sample block. The method furtherincludes lifting the sample well tray holder and sample well tray fromthe heating device by a biasing mechanism so that the sample well trayis capable of rotation away from the sample block and heating devicewithout interference, and then rotating the sample well tray holder ofthe first robot mechanism in a second rotational direction toward thefirst position to remove the sample well tray holder from the heatingdevice. The sample well tray may then be removed from the sample welltray holder. The method further includes, prior to placing the samplewell tray in a sample well tray holder, the steps of picking up a samplewell tray with a second robot mechanism, such as a rotational robot, androtating the sample well tray to place the sample well tray in the firstposition.

[0012] It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive of the invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The accompanying drawings, which are incorporated in andconstitute a part of this specification, illustrate several embodimentsof the invention and together with the description, serve to explain theprinciples of the invention. In the drawings, FIG. 1 shows a perspectiveview of a sample well tray handling apparatus according to theinvention;

[0014]FIG. 2 shows a top view of the sample well tray handling apparatusof FIG. 1;

[0015]FIG. 3 shows a sectional view of the sample well tray handlingapparatus along line Ill-Ill of FIG. 2;

[0016]FIG. 4 shows a perspective view of a sample well tray holder ofthe sample well tray handling apparatus of FIG. 1;

[0017]FIG. 5 shows a top view of a system including the sample well trayhandling apparatus of FIG. 1 in addition to a heating device and arobot, the sample well tray handling apparatus in a first position forhaving a sample well tray transferred from the robot;

[0018]FIG. 6 shows a top view of the system of FIG. 5, the sample welltray handling apparatus rotated relative to the first position of FIG. 5so that the sample well tray is located in the heating device;

[0019]FIG. 7 shows a side view of an urging mechanism positioned on abottom surface of the sample well tray holder of FIG. 1;

[0020]FIG. 8 is a bottom view of the urging mechanism of FIG. 7;

[0021]FIG. 9A is a schematic sectional view illustrating a cover andsample well tray in an open position; and

[0022]FIG. 9B is a schematic sectional view illustrating the cover andsample well tray of FIG. 9A in a closed position.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Reference will now be made in detail to the present preferredembodiments of the invention, examples of which are illustrated in theaccompanying drawings. Wherever possible, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

[0024] In accordance with the present invention, an apparatus fortransporting sample well trays with respect to a heating device isprovided. In certain embodiments of the present invention, the apparatusincludes a sample well tray holder, a rotational actuator configured torotate the sample well tray holder, and a biasing mechanism configuredto urge the sample well tray holder in a generally upward direction. Incertain embodiments, the invention is directed toward a system whichadditionally includes a robot device for transporting a sample well trayto the sample well tray holder, and a heating device with an opening forreceiving the sample well tray therein. As embodied herein and shown inFIGS. 1-9, the handling apparatus 10 for transporting sample well traysincludes a sample well tray holder 12, a rotational actuator 14, and abiasing mechanism 16.

[0025] Handling apparatus 10 may be used to load and unload sample welltrays into a wide variety of types of heating devices. In certainembodiments, the heating device may be a PE Biosystems 5700 and 7700Detection Instrument, as well as a variety of other types ofinstruments. One example of a suitable heating device is described inU.S. Pat. No. 5,928,907 to Woudenberg et al., which is assigned to theassignee of the present invention, the contents of which are herebyincorporated by reference herein for any purpose. The heating device 100shown in FIGS. 5-6 is preferably configured for use with 96-well and384-well sample trays, in addition to microcard sample trays. Oneexample of a 384-well sample tray is illustrated in FIGS. 9A and 9B as asample well tray 208 with a plurality of sample wells 210. Examples ofsample well trays suitable for use in the apparatus of the presentinvention are described in WO00/25922 to Moring et al., which isassigned to the assignee of the present invention, the contents of whichare hereby incorporated by reference herein for any purpose. Examples ofmicrocard sample trays suitable for use in the apparatus of the presentinvention are described in WO97/36681 to Woudenberg et al., which isassigned to the assignee of the present invention, the contents of whichare hereby incorporated by reference herein for any purpose. Sample welltrays having any number of sample wells and sample well sizes may alsobe used. In the example shown in the figures, the volume of the samplewells may vary anywhere from 0.01 μl to thousands of microliters (μl),with a volume between 10 to 500 μl being typical. The detectioninstrument may be used for a variety of applications, such as, but notlimited to, fluorescent PCR-based detection.

[0026] As embodied herein and shown in FIGS. 5, 6, 9A, and 9B, theheating device 100 includes a sample block 102 or other type of surfacefor receiving a sample well tray, such as sample well tray 208, from thehandling apparatus 10. As shown in FIGS. 5, 6, 9A, and 9B, sample block102 includes a plurality of openings 104 in a top portion thereof forreceiving sample wells 210 of the sample well tray. Each of the sampleblock openings 104 may have a conical shape which is sized to fit with asample well of a sample well tray. The sample block openings may beother shapes such as cylindrical or hemispherical, depending on theshape of the mating sample wells. Sample blocks are well known in theart. The sample block will typically have openings of a number matchingthe number of sample wells of the sample well tray. The sample blockshown in FIG. 5 has 384 openings arranged in a 16×24 array, however, anynumber of openings may be provided. Other common configurations include96 and 60-well sample blocks, although the present invention is suitablefor sample well trays having anywhere from one sample well to severalthousand sample wells. The sample block is preferably constructed of aheat-conducting material such as gold-plated silver and aluminum,although other common materials may also be it suitable.

[0027] Likewise, although the description discusses trays with samplewells, the present invention is suitable for use with sample trays thatdo not include wells. These trays may have a flat surface on which asample of biological material is placed. The flat surface on which thesample is placed may be similar to a microscope slide for a sample. Inthis type of sample tray, a liquid may be dropped onto the tray at aplurality of positions, and then a film or cover positioned on the topsurface of the tray over the samples. Alternately, a sample tray mayinclude a porous material such a frit on the top surface, instead ofsample wells, for holding samples of biological material. Therefore,although the description refers to sample well trays throughout, itshould be understood that the present invention is also suitable forsample trays that do not have sample wells.

[0028] The heating device 100 further includes a cover which lowers andapplies pressure to the top of the sample well tray after the samplewell tray is inserted into the heating device. In an exemplaryembodiment shown in FIGS. 9A and 9B, a heated cover 150 includes acentral cover portion 152 and an outer cover portion 154. In theembodiment shown in FIGS. 9A and 9B, the central cover portion 152 has aplurality of openings 156 for the optical detection of reactions thatoccur in the sample wells of the sample well tray. The present inventionis also suitable for use in a thermal cycler or other heating apparatuswithout optical detection capabilities. In one embodiment, the outercover portion 154 is movable in an upward and downward directionrelative to the central cover portion 152. The cover may be any of avariety of types. For example, in certain embodiments, the cover isphysically actuated to and from a closed position by a motor. In otherembodiments, the cover is slid into and out of a closed position bymanual physical application. The cover may also include at least oneheated platen (not shown) for pressing against the top surface of thesample well trays in order to reduce condensation from occurring on thesample well trays.

[0029] The handling apparatus 10 may receive the-sample well trayseither-manually or automatically. In certain embodiments, the handlingapparatus 10 receives sample well trays from a robot, such as robot 200shown in FIGS. 5 and 6. The robot 200 may be any type of robot, such asa rotational robot that rotates about a single axis 202. One example ofa rotational robot that is suitable for use with the handling apparatus10 is a Zymark™ Twister robot. In certain embodiments, the robot 200includes an arm 204 and a robot hand 206 for gripping a sample well tray208. The rotational robot picks up a single sample well tray 208 andthen rotates about the rotational axis 202 to bring the sample well trayto the position shown in FIG. 5. In the position shown in FIG. 5, thesample well tray 208 may be transferred to handling apparatus 10. Thehandling apparatus 10 then inserts the sample well tray into sampleblock 102 of heating device 100 as shown in FIG. 6 and the samples inthe sample well tray are thermally cycled. The handling apparatusremoves the sample well tray from the heating device and rotates back toFIG. 5 so that the sample well tray may be picked up from the handlingapparatus by the robot 200. The heating device may be any type known inthe art. The specific heating devices discussed in relation to thepresent invention are described for purposes of illustration only.

[0030] The present invention is directed at the handling apparatus, aswell as the overall system. In accordance with the present invention,the handling apparatus 10 includes a sample well tray holder 12 forsupporting a sample well tray therein. As embodied herein and shown inFIGS. 1-4, the sample well tray holder 12 is in the shape of a flatplate with a main body portion 20 and an arm portion 22. In the exampleshown in the figures, the main body portion 20 is in a rectangularshape. The main body portion 20 defines a rectangular opening or recess24 sized and shaped for receiving a sample well tray. The sample welltray holder is preferably made out of a material with poor heatconduction characteristics and a low thermal mass. In certainembodiments, the material selected for the sample well tray holder is apolycarbonate. Other suitable materials are also acceptable, including ahybrid metal/plastic sample tray holder.

[0031] The rectangular opening 24 of the sample well tray holder isconfigured so that the sample well tray 208 may rest on the sample welltray holder. The rectangular opening 24 is defined by a tapered wall 26which tapers downward from the top surface 28 of the sample well trayholder 12. The tapered wall 26 tapers until it meets a floor portion 30which extends from the tapered wall. The floor portion 30 generallyextends along a bottom surface of the sample well tray holder. The floorportion 30 defines a rectangular opening that is smaller than the sizeof a sample well tray. Therefore, when a sample well tray is placed inthe rectangular opening 24, a bottom surface 212 of outer side walls 214of the sample well tray 208 rest on a top surface of the floor portion30, as best illustrated in FIG. 9A. The provision of the tapered wall 26permits the sample well tray 208 to center itself in the rectangularopening 24 as the sample well tray is placed in the rectangular opening.

[0032] In certain embodiments, the arm portion 22 of the sample welltray holder 12 projects on the same plane as the main body portion 20.In the embodiment shown in FIGS. 1-9, the arm portion includes aplurality of fasteners 32 such as bolts for fastening the sample welltray holder 12 to an extension arm 34 which is connected to therotational actuator 14 and biasing mechanism 16. As shown in FIG. 3, theextension arm 34 is a flat plate with a thin lower portion 36 on whichthe arm portion 22 of the sample well tray holder may be mounted. Thefasteners 32 pass through the arm portion 22 of the sample well trayholder 12 into a threaded connector 38 on the thin lower portion 36 ofthe extension arm. The arm portion 22 of the sample well tray holder 12and the extension arm 34 are preferably configured so that there isminimal movement between the arm portion 22 and extension arm 34. Incertain embodiments, the ends of the arm portion 22 and extension arm 34are flat surfaces that abut against each other as shown in FIG. 2.Additionally, in certain embodiments, the sample well tray holder mayinclude one or more holes to engage with pins in the thin lower portion36 of extension arm 34. In one embodiment, illustrated for example inFIGS. 1 and 2, the sample well tray holder includes a locating hole 29and a locating slot 31 for engaging with pins projecting from the topsurface of the thin lower portion 36 of extension arm 34. Alternately,the arm portion 22 and extension arm 34 could be an integral piece,thereby reducing the number of parts for the apparatus.

[0033] In other embodiments, the connection between the arm portion 22and extension arm 34 may be configured so that the arm portion 22 isadjustable on the extension arm 34. In such a configurations, the armportion or extension arm might include two parallel slots for aconnector so that the arm distance may be adjusted.

[0034] The sample well tray holder 12 may further include an urgingmechanism for urging the sample well tray away from the sample blockupon opening of the cover. As embodied herein and shown in FIG. 3, theurging mechanism may include any suitable type of mechanism such as aspring device for pressing upward on the sample holder and sample welltray when the cover is opened. In the example shown 1-8, the urgingmechanism includes a plurality of springs 40 positioned on the bottomsurface 42 of the sample well tray holder 12. As shown in FIGS. 3, 7,and 8, the springs 40, in one example, may be a strip of folded springscommonly referred to as RF gaskets, positioned in parallel relationshipto each other. The base 44 of each spring may be attached to the bottomsurface 42 of the sample well tray holder 12 by adhesive 46 or any othersuitable attachment method. The spring portion 48 of the spring 40includes a curved member that imparts an upward force on the sample welltray holder 12 when it is compressed.

[0035] Although the urging mechanism is shown as being an RF gasket inthe figures, any other type of suitable urging mechanism may alternatelybe used. Examples of other types of urging mechanism are described inco-pending U.S. application Ser. No. 09/496,408, filed Feb. 2, 2000,assigned to the assignee of the present application, the contents ofwhich are hereby incorporated by reference herein. The urging mechanismof the present invention may be made out of any of a variety of forceimparting devices such as one or more coil springs, leaf springs,hydraulic dampeners, elastomeric springs, or other conventional springdevices. The urging mechanism is typically designed to providesufficient force to overcome the sticking force between the sample welltray and the sample block upon opening of the cover of the heatingdevice. Sticking may result because of deformation of the sample welltray during heating. In one example, the urging mechanism imparts anupward force on the sample well tray holder of approximately 15-20 lbs.The amount of force required depends on the specific application. Theurging mechanism should preferably loosen the sample well tray from thesample block so that the sample well tray can be easily removed eitherrobotically or manually.

[0036] In certain embodiments, particularly those with sample wellshaving relatively small volumes, it may be desirable to place a thincompliant cover (not shown) between central cover portion 152 and thetop of sample well tray 208. An example of a suitable compliant cover isdisclosed in the specification and figures (FIGS. 11-13) of co-pendingU.S. application Ser. No. 09/499,408, the contents of which areincorporated by reference herein. The compliant cover typically includesdetection holes aligned with each of the sample wells 210 of the samplewell tray. The compliant cover may assist in evenly distributing thedownward force imparted by the cover onto the sample well tray. Inembodiments with a compliant cover, it may be helpful to further providea boss or rib (not shown) on the top surface 28 of the main body portion20 of sample well tray holder 12 for engaging with the bottom surface ofouter cover portion 154 when the outer cover portion 154 is loweredrelative to the central cover portion 152. An example of a suitable bossor rib to be used in conjunction with the compliant cover is disclosedin the specification and figures (FIGS. 11-13) of co-pending U.S.application Ser. No. 09/499,408, the contents of which are incorporatedby reference herein The downward movement of the outer cover portion 154results in the outer cover portion 154 pressing downward on the mainbody portion 20 of sample tray holder 12 so that the upper surface ofthe floor portion 30 of the sample tray holder will become spaced fromthe bottom surface 212 of the sample well tray 208. This spacing betweenthe sample well tray and the surface of the floor portion of the sampletray holder isolates the sample well tray 208 from the spring forcegenerated by the springs 40 of the urging mechanism. In certainembodiments, this configuration assists in eliminating the upward forceof the springs 40 from the sample tray in order to reduce the amount ofvolume loss due to bending of the sample tray.

[0037] In certain embodiments of the present invention, the handlingapparatus 10 removes the sample well tray robotically after the urgingmechanism has loosened the sample well tray from the sample block.Alternately, in certain embodiments, urging mechanisms of the typedescribed above could be attached to the sample block instead of thebottom surface of the sample well tray holder. In other embodiments, theurging mechanism may be entirely eliminated because the biasingmechanism 16 (to be described in greater detail later) will providesufficient force to loosen the sample well tray from the sample block.

[0038] In accordance with the present invention, the handling apparatus10 includes a rotational actuator for rotating the sample well trayholder about a first rotational axis, and a biasing mechanism configuredto urge the sample well tray holder in a generally upward directionalong the first rotational axis. As embodied herein and shown in FIGS.1-8, a rotational actuator 14 is provided for rotating the sample welltray about rotational axis 50. As shown in FIGS. 1-9, the rotationalactuator 14 includes a motor 52, a spline shaft 54, and a spline bushing56. The rotational actuator allows the handling apparatus 10 to berotated about an axis so that the sample well tray may be transportedbetween at least two predetermined positions.

[0039] In the example shown in FIGS. 1-9, the motor 52 may be any typeof motor capable of providing sufficient force to rotate the sample welltray holder 12 through an approximately 90 degrees rotation. In certainembodiments, the motor is a stepper motor. Other types of rotationalforce generating devices such as servo motors (with an encoder), rotarysolenoids, spring loaded devices, etc. may also be used. In one example,the motor is a 5 volt, 1 amp stepper motor rated at 200 steps perrevolution, which may be micro-stepped to provide 1,600 steps perrevolution. It is preferable that the motor be controlled accurately sothat it provides precise rotation of the sample well tray holder from afirst position to a second position, and back to the first position.

[0040] In certain embodiments, a rotational position sensing device maybe provided in order to enhance the accuracy of the rotational actuator.For example, a rotational position sensing device 58 such as a rotaryencoder may be used to control the amount of rotation of the motor. Incertain embodiments, the rotational position sensing device includes asensor 60 that detects the number of slots 62 on a disk 64 that haverotated past the sensor. Other types of rotational position sensingdevices are known in the art, and are suitable with the presentinvention.

[0041] As shown in FIG. 3, motor output shaft 65 of motor 52 may beattached to a second shaft such as a spline shaft 54. In the exampleshown, spline shaft 54 transmits rotational movement to a spline bushing56 positioned around the spline shaft. The spline shaft 54 transmitsrotation to the spline bushing 56 while still allowing relative axialmovement between the spline bushing and spline shaft. The spline shaftand bushing are configured so that the spline bushing may move axiallyalong the spline shaft, but remain rotationally fixed to the splineshaft. In certain embodiments, a ball spline and bushing are employed tominimize rotational backlash in the mechanism. Other configurations suchas a simple spline configuration with an axial projection and a grooveare also suitable with the present invention.

[0042] As best shown in FIG. 3, the spline bushing 56 includes anaxially extending cylindrical member 66 and a flange member 68 at an endthereof. In the example shown, flange member 68 has an outer diametergreater than the axially extending cylindrical member 66. In certainembodiments, flange member 68 of the spline bushing, which is in theshape of a disk, includes a plurality of holes 70 for receiving bolts tofasten the spline bushing 56 to the extension arm 34. In the embodimentshown in FIGS. 1-8, spline bushing 68 includes four holes 70 throughwhich bolts 72 may pass through into mating holes 74 in the extensionarm 34. As shown in FIG. 3, extension arm 34 is configured to include ahole 35 with an inside diameter corresponding to the outside diameter ofthe axially extending cylindrical member 66 of the spline bushing.Alternately, the extension arm 34 may be attached to the spline bushingby any number of conventional methods, or could be made integral withthe spline bushing.

[0043] As shown in FIGS. 1-3 and 5-6, a cylindrical stop member 80 isattached to the end of the spline shaft 54. The cylindrical stop member80 prevents the spline bushing 56 from moving axially along therotational axis 50 beyond a predetermined point. The cylindrical stopmember 80 may be any structure that prevents the spline bushing 56 frommoving axially beyond a predetermined point. In the embodiment shown inFIGS. 1-9, the cylindrical stop member is an annular member with anannular recess or counterbore 82 matching the outer diameter of thespline shaft 54. The cylindrical stop member 80 may be attached to theend of the spline shaft 56 by any known method, such as fasteners,threads, interference fit, glue, etc.

[0044] The spline bushing may move axially downward on the spline shaftalong axis 50. A biasing mechanism 16 is provided to urge-the splinebushing in an upward direction to resist movement of the spline bushingin the downward direction in FIG. 3. The biasing mechanism 16 isconfigured to urge the sample well tray holder 12 and sample well tray208 away from the sample block 102 when the cover of the heating device100 is opened. As embodied herein and shown schematically in FIGS. 1 and3, a spring device such as a helical spring 84 is provided. It should beunderstood that helical spring 84 is shown schematically for purposes ofillustration only. The helical spring may be a variety of sizes andspring constants, depending on the size constraints and the amount offorce desired. In one embodiment, the helical spring is approximately1.75 inches in length, and 1.0 inch in diameter.

[0045] In the embodiment of FIGS. 1-9, helical spring 84 is positionedconcentric to the rotational axis 50 and surrounds a portion of thelength of the spline shaft 54. A bottom annular stop member 86 ispositioned on an opposite end of the spline shaft 54 than cylindricalstop member 80. The bottom annular stop member 86 is provided on thespline shaft 54 as shown in FIG. 3, and is in the shape of a disk withan inside bore mating with the outer surface of the spline shaft 54. Inthe embodiment shown, the annular stop member also includes acounterbore 88 on the top surface thereof for engaging an outerperiphery of the bottom portion of the helical spring 84. Thecounterbore assists in provide a reliable securement of the bottom endof the helical spring. Likewise, the bottom surface 90 of the extensionarm 34 includes a counterbore 92 for engaging an outer periphery of thetop end of the helical spring 84.

[0046] Other types of biasing mechanisms such as elastomeric sleeves maybe used instead of helical springs. One or several spring devices suchas leaf springs, conical helical springs, elastomers, and other springswhich impart an axial force when compressed are also suitable with thepresent invention. In addition, other spring-like devices suitable foruse in the present invention include, for example, air cylinders, fluidcylinders, dampeners, belleville washers, and electrical solenoids. Thesize and type of spring device depend on the specific design constraintsof the handling apparatus.

[0047] Helical springs, also called coil springs, such as shown in thefigures are particularly suitable in applications where relatively largecompression stroke lengths are desired, whereas an elastomeric sleevemay be suitable if short compression stroke lengths are preferred. Inone example, the helical spring 84 is compressed about 0.5 inches. Inapplications with a large compression stroke for the biasing mechanism,a helical spring may be better suited than an elastomeric sleeve. Thebiasing mechanism is typically configured so that the sample well traymay be pushed downward a slight distance by the cover of the heatingdevice after the sample well tray is aligned with the sample block. Asshown for example in FIG. 9B, the cover 150 of the heating devicetypically presses downward on the sample well tray 208 so that thesample wells 210 of the sample well tray are firmly pressed againstsurfaces of the sample block openings 104 in the sample block 102.

[0048] As the sample well tray holder is pressed downward, the helicalspring 84 is compressed a slight distance. Because the spring constantof the helical spring is small relative to the downward force of thecover, the upward force imparted by the helical spring will not bend thesample well tray. The force imparted by the helical spring of thebiasing mechanism will be sufficient to lift the loosened sample welltray away from the sample block, after the urging mechanism has loosenedthe sample wells from the sample block openings, so that the bottoms ofthe sample wells 210 do not interfere with the corresponding openings104 in the sample block. FIG. 9A shows the position of the sample welltray after the biasing mechanism lifts the sample well tray from thesample block. In one example, the biasing mechanism imparts an upwardforce of approximately six lbs on the sample well tray holder. Thebiasing mechanism cooperates with the springs 40 of the urging mechanismto lift the sample well tray completely out of the sample block recessesafter the springs 40 of the urging mechanism have overcome the stickingforce between the sample wells and the sample block.

[0049] The operation of the handling apparatus for one typicalembodiment corresponding to FIGS. 1-9 will now be more completelydescribed below. First, a robot such as rotational robot 200 shown inFIG. 5 grasps a sample well tray 208 with a grasper such as robot hand206. The robot arm 204 and robot hand 206 then rotate the sample welltray about rotational axis 202 to the position shown in FIG. 5. Therotational robot 200 opens robot hand 206 to drop the sample well tray208 into the rectangular opening 24 of the sample well tray holder 12 ofthe handling apparatus 10. As shown in FIG. 5, the handling apparatus 10is located in a first position so that the rectangular opening 24 isaligned with the sample well tray 208 in the robot hand 206. Preferably,the rectangular opening 24 includes tapered walls so that the samplewell tray 208 slides downward into the rectangular opening 24 of samplewell tray holder 20 and is centered in the rectangular opening.

[0050] After the sample well tray 208 is seated in the rectangularopening 24 of the sample well tray holder 12, the rotational actuator 14of the handling apparatus 10 rotates the sample well tray holder 12about rotational axis 50 from a first position shown in FIG. 5 to asecond position shown in FIG. 6. In the rotational actuator describedabove, for example, motor 52 rotates motor output shaft 65 and splineshaft 54. Spline shaft 54 transmits torque to spline bushing 56 andextension arm 34. The extension arm 34 is connected to arm portion 22 ofsample well tray holder 12 and transmits rotational motion to the samplewell tray holder 12. The sample well tray holder 12 is thereby rotatedapproximately ninety degrees about rotational axis 50 from the firstposition shown in FIG. 5 to a second position shown in FIG. 6. This is aclockwise rotation as viewed in FIGS. 5 and 6.

[0051] At the second position shown in FIG. 6, the sample well tray 208is roughly aligned with the sample block 102 of heating device 100. Eachof the plurality of sample wells 210 of the sample well tray are alignedwith a respective opening 104 in the sample block, as shown for examplein FIG. 9A. The sample well tray 208 is initially positioned over thesample block 102 at a first height so that the sample wells of thesample well tray have clearance over the sample block so that the samplewell tray holder can be swung into position. This initial position isshown for example in FIG. 9A.

[0052] A cover 150 of the heating device, initially positioned over thesample well tray may then be lowered, pressing against the top surfaceof the sample well tray and sample well tray holder so that the samplewells of the sample well tray 208 are lightly pressed against therecesses of the sample block 102. As the sample well tray holder lowersto this second height, the helical spring 84 of the biasing mechanism 16is compressed. The spline bushing 56 is thereby lowered so that a spaceis created between the top of the spline bushing and the bottom surfaceof stop member 80. As the cover 150 continues to be lowered, the springs40 of the urging mechanism are then compressed until the sample welltray holder 20 reaches a third height shown in FIG. 9B, and the cover iscompletely closed. At this third height shown in FIG. 9B, the samplewells 210 of the sample well tray 208 are firmly pressed against theopenings 104 of the sample block.

[0053] The heating device, such as thermal cycler 100, thereafter heatsthe liquid sample in the sample well tray to undergo a PCR or other typeof chemical reaction. After the thermal cycling and/or other operationsare completed, the cover 150 is opened. As the cover is opened, thecover will no longer press against the top of the sample well tray.Simultaneously, the springs 40 of the urging mechanism will impart anupward force on the bottom surface 42 of the sample well tray, therebyurging the sample wells 210 upward so that they no longer press againstthe surface of the openings 210 of the sample block. The springs shouldimpart sufficient force so that the sample well tray becomes loosenedfrom the sample block. At this second height, the sample wells are stillpositioned in the recesses in the sample block, consequently, the samplewell tray holder cannot be rotated away from the sample block withoutinterfering with the sample block.

[0054] The provision of the biasing mechanism 16 permits for theimmediate raising of the sample well tray out of the sample block abovethe second height. Helical spring 84 of biasing mechanism 16 pressesupward on the spline bushing 56 so that the sample well tray holderreturns to its first height (FIG. 9A). At the first height, the top ofthe spline bushing 56 typically abuts a bottom surface of the stopmember 80. The first height corresponds to a height at which the samplewell tray can be rotated away from the sample block withoutinterference. This is shown for example in FIG. 9A. Consequently, thesample well tray holder 12 can now be rotated from the second positionshown in FIG. 6 to the first position shown in FIG. 5 by the rotationalactuator.

[0055] The rotational actuator rotates the sample well tray holder inthe opposite direction (counterclockwise as viewed in FIGS. 5 and 6) asit was previously rotated. When the sample well tray holder and samplewell tray are returned to the first position shown in FIG. 5, the robothand 206 of the robot 200 may grasp the sample well tray 208 and removeit from the sample well tray holder 12. Thereafter, the robot 200 mayrotate and bring the sample well tray to a receiving position, forexample, a position on the robot. The robot 200 may then grab anothersample well tray on or adjacent the robot, within the radius of therobot arm, and repeat the above operation.

[0056] As is clear from the above description, the present inventionincludes a method of manipulating sample well trays. The method includesthe step of placing the sample well tray into a sample well tray holderof a first robot mechanism located at a first position. The methodfurther includes the step of rotating the sample well tray holder of thefirst robot mechanism about a rotational axis in a first rotationaldirection to insert the sample well tray holder into a heating device ata second position. The sample well tray engages with a cover of theheating device to lower the sample well tray holder in a directiontoward a sample block of the heating device so that the sample wells ofthe sample well tray firmly engage the corresponding openings in thesample block. The sample well tray then undergoes a heating operationsuch as thermal cycling. After the heating operation is completed, thecover of the heating device is opened so that the sample well tray andsample wells disengage from the sample block. As a result, the samplewell tray no longer directly contacts the sample block. The methodfurther includes lifting the sample well tray holder and sample welltray from the sample block openings by a biasing mechanism so that thesample well tray is capable of rotation away from the sample block andheating device without interference. The sample well tray holder is thenrotated in a second rotational direction toward the first position toremove the sample well tray holder from the heating device. The methodfurther comprises, prior to placing the sample well tray in a samplewell tray holder, the steps of picking up a sample well tray with asecond robot mechanism, such as a rotational robot, and rotating thesample well tray to place the sample well tray in the first position.

[0057] The system and method according to the present invention may beused to transport a large number of sample well trays into a thermalcycler having detection capabilities. This may increase throughput andimprove safety for operators of thermal cyclers. With such a handlingapparatus, it is unnecessary to manually load the sample well trays intoa thermal cycler.

[0058] It will be apparent to those skilled in the art that variousmodifications and variations can be made in the apparatus and method forhandling sample well trays, use of the apparatus of the presentinvention, and in construction of this apparatus, without departing fromthe scope or spirit of the invention.

[0059] Other embodiments of the invention will be apparent to thoseskilled in the art from consideration of the specification and practiceof the invention disclosed herein. It is intended that the specificationand examples be considered as exemplary only, with a true scope andspirit of the invention being indicated by the following claims.

What is claimed is:
 1. An apparatus for transporting sample well trayswith respect to a heating device, comprising: a sample well tray holdercomprising a plate in which a sample well tray may be positioned, saidsample well tray holder configured to rotate about a first rotationalaxis; a rotational actuator configured to rotate the sample well trayholder about the first rotational axis; and a biasing mechanismconfigured to urge the sample well tray holder in a generally upwarddirection along the first rotational axis.
 2. The apparatus of claim 1,wherein the rotational actuator comprises a motor.
 3. The apparatus ofclaim 2, wherein the motor is configured to rotate the sample well trayholder approximately ninety degrees.
 4. The apparatus of claim 2,wherein the rotational actuator further comprises a shaft attached tothe motor.
 5. The apparatus of claim 4, wherein the motor comprises astepper motor.
 6. The apparatus of claim 4, wherein the shaft attachedto the motor is a spline shaft, the rotational actuator furthercomprising a spline bushing for engaging with the spline shaft so thatthe spline bushing is rotationally fixed but axially moveable relativeto the spline shaft.
 7. The apparatus of claim 6, wherein the splinebushing is rotationally fixed to the sample well tray holder.
 8. Theapparatus of claim 7, further comprising an extension arm for attachingthe spline bushing to the sample well tray holder.
 9. The apparatus ofclaim 1, wherein the plate of the sample well tray holder includes arecess for positioning the sample well tray therein.
 10. The apparatusof claim 9, wherein the recess is defined by tapered side walls forreceiving the sample well tray, the tapered side walls configured sothat the sample well tray rests on the tapered side walls.
 11. Theapparatus of claim 10, wherein the recess is rectangular.
 12. Theapparatus of claim 9, wherein the plate of the sample well tray holderincludes a first portion having the recess and a second portioncomprising an arm for connecting the first portion with the rotationalactuator.
 13. The apparatus of claim 1, wherein the biasing mechanismcomprises a spring member.
 14. The apparatus of claim 13, wherein therotational actuator further comprises an output shaft that is rotatablyfixed relative to the sample well tray holder, the spring membercomprising a helical spring positioned around the first rotational axisand the output shaft.
 15. The apparatus of claim 7, wherein the biasingmechanism comprises a helical spring positioned around the firstrotational axis and surrounding a portion of the spline bushing.
 16. Theapparatus of claim 1, further comprising a robot configured to grasp asample well tray and transport the sample well tray to the sample welltray holder.
 17. The apparatus of claim 1, further comprising a heatingdevice with an opening for the sample well tray to be placed therein.18. The apparatus of claim 1, further comprising a heating device forconducting thermal cycling.
 19. The apparatus of claim 18, wherein thethermal cycling results in nucleic acid amplification.
 20. The apparatusof claim 1, wherein the sample well tray comprises a 96-well microtitertray.
 21. The apparatus of claim 1, wherein the sample well traycomprises a 384-well microtiter tray.
 22. The apparatus of claim 1,wherein wells of the sample well tray are conical.
 23. The apparatus ofclaim 1, wherein wells of the sample well tray are sized to have a fluidvolume in the range of 10 to 500 μl.
 24. A robotic manipulator fortransporting sample well trays between at least two positions,comprising: a robotic arm having a sample well tray holder configured tosupport a sample well tray therein, the sample well tray holdercomprising a recess for the sample well tray; a rotational mechanismconfigured to impart rotational motion on the robotic arm, therotational mechanism comprising a motor; and a biasing mechanismconfigured to provide force on the sample well tray holder in adirection away from an adjacent sample block.
 25. The roboticmanipulator of claim 24, wherein the biasing mechanism comprises atleast one helical spring positioned partially surrounding a shaft of therotational mechanism.
 26. The robotic manipulator of claim 25, furthercomprising a sleeve member positioned around the shaft of the rotationalmechanism and partially surrounded by the helical spring, the sleevemember being rotationally fixed to the shaft of the rotational mechanismand axially slidable relative to the shaft, the biasing mechanismconfigured to urge the sleeve member in the direction away from theadjacent sample well block.
 27. The robotic manipulator of claim 25,wherein the sleeve member comprises a spline bushing configured toengage a spline on the shaft of the rotational mechanism.
 28. Therobotic manipulator of claim 26, further comprising a stop memberpositioned on the shaft of the rotational mechanism, the stop memberconfigured to prevent the sleeve member from axially moving beyond apredetermined position on the shaft of the rotational mechanism.
 29. Asystem for manipulating sample well trays, comprising: a robotconfigured to transport a sample well tray to a first location; aloading mechanism configured to take a sample well tray from the firstlocation, place the sample well tray into a heating device at a secondlocation and then later remove the sample well tray from the heatingdevice and return the sample well tray to the first location, theloading mechanism comprising a sample well tray holder in which a samplewell tray may be positioned therein, a rotational actuator configured torotate the sample well tray holder, and a biasing member configured tourge the sample well tray and sample well tray holder in a directionaway from a sample block; and a heating device having an opening forreceiving the sample well tray therein.
 30. The system of claim 29,wherein the heating device is a heater and the rotational actuatorcomprises a motor for rotating a shaft and a spline bushing positionedin a rotationally fixed manner on the shaft.
 31. A method ofmanipulating sample well trays, comprising: placing a sample well trayinto a sample well tray holder of a first robot mechanism located at afirst position; rotating the sample well tray holder of the first robotmechanism about a rotational axis in a first rotational direction toinsert the sample well tray holder into a heating device at a secondposition; lowering the sample well tray holder in a direction toward asample block of the heating device so that the sample well tray engagesthe sample block; disengaging the sample well tray from the sample blockso that the sample well tray does not directly contact the sample block;lifting the sample well tray holder and sample well tray from theheating device by a biasing mechanism so that the sample well tray iscapable of rotation away from the sample block and heating devicewithout interference; and rotating the sample well tray holder of thefirst robot mechanism in a second rotational direction toward the firstposition to remove the sample well tray holder from the heating device.32. The method of claim 31, wherein the lowering of the sample well trayholder comprises engaging the sample well tray with a cover of theheating device in order to lower the sample well tray holder.
 33. Themethod of claim 31, further comprising, prior to placing the sample welltray in a sample well tray holder, the step of picking up a sample welltray with a second robot mechanism, and rotating the sample well tray toplace the sample well tray in the first position.
 34. The method ofclaim 31, wherein the biasing mechanism that lifts the sample well trayholder comprises a helical spring that urges the sample well tray awayfrom the sample block.
 35. The method of claim 31, wherein the step ofdisengaging the sample well tray from the sample block includesproviding an upward force on the sample well tray holder by an urgingmechanism positioned between the sample well tray holder and the sampleblock.
 36. The method of claim 35, wherein the urging mechanismcomprises at least one spring device.